Biphasic foam blood mass transfer device

ABSTRACT

The present invention relates to apparatus for transferring constituents into and out of a fluid such as blood. The apparatus includes a biphasic foam body which functions as a blood oxygenator, blood dialyzer, or other blood mass transfer device.

FIELD OF THE INVENTION

The present invention relates to apparatus for transferring constituentsinto and out of blood. More particularly, the invention uses a biphasicfoam as a blood oxygenator or dialyzer.

BACKGROUND OF THE INVENTION

The field of this invention is blood mass transfer devices, particularlyoxygenators, wherein some desirable constituent (e.g., oxygen) istransferred into the blood and/or some undesirable constituent (e.g.,carbon dioxide) is transferred out of the blood. Three basic types ofoxygenators have developed over time: film oxygenators (e.g., U.S. Pat.No. 3,070,092), bubble oxygenators (e.g., U.S. Pat. Nos. 3,915,650 and4,428,934); and membrane oxygenators (e.g., U.S. Pat. No. 4,698,207).

Film oxygenators are characterized by exposing a continuous thin film ofblood to an oxygen atmosphere. The surface upon which the blood isfilmed must be chemically inert and not damage the blood. Additionally,the surface must sustain a very thin film in order to maximize thediffusion of oxygen into the blood. In bubble oxygenators, oxygen isintroduced into the blood as bubbles which oxygenate the blood and driveoff carbon dioxide. In these oxygenators, the bubbling or foamingmixture must be passed through a "defoamer" to eliminate gas bubblesfrom the oxygenated blood before it is returned to the patient. In atypical membrane oxygenator, blood is carried in or around hollowmembrane fibers. Oxygen passes through the membrane from an oxygen-richgas stream to the bloodstream, and carbon dioxide passes through themembrane from the blood to the gas stream. The number and size of thehollow membrane fibers are selected to transfer sufficient oxygen tosatisfy the metabolic requirements of the patient. Before the blood isreturned to the patient from the membrane oxygenator, it is usuallypassed through a filter to remove any particulate emboli or gas bubbles.The filter is usually in the arterial line outside of the oxygenatoritself.

Various types and configurations of foam have been used for specificpurposes in bubble and film oxygenators. Blood oxygenators which usefoam material to "defoam" the blood-oxygen mixture, i.e., remove bubblesfrom the blood, are well known as illustrated by the blood oxygenator inU.S. Pat. No. 4,158,693 to Reed et al. Foam material is also used in theReed et al. bubble oxygenator to provide an enlarged surface area foroxygen-blood contact, and to disperse the blood so it will riseuniformly through the oxygenating chamber. The film oxygenator in U.S.Pat. No. 3,070,092 to Wild et al. uses a porous sponge material as thesurface on which the blood is filmed. None of these types of oxygenatorscontemplates using a foam material as both the blood pathway and themembrane across which oxygenation occurs.

Certain parameters must be considered when designing an oxygenator,whether of the film, bubble, or membrane type. Parameters which must beconsidered include the overall size and geometry of the oxygenator,blood volume that can be oxygenated, damage to the blood, the rate ofgas exchange, and the volume of blood physically held by the oxygenator(known as "priming volume").

The physical size of an oxygenator is determined in large part by theeffective exchange surface area, that is, the exchange surface area theblood is exposed to for oxygenation. The total volume of blood that canbe oxygenated must be sufficient to satisfy the metabolic requirementsof a patient. As discussed in U.S. Pat. No. 4,698,207 to Bringham etal., this can require using 41,000 to 71,000 hollow fibers in a hollowfiber membrane oxygenator. In order to minimize the size of a bloodoxygenator, a large exchange surface area must be contained in a smallvolume. As a result, the exchange surface area may have to assumeintricate geometries which is made difficult by the structures ofconventional membrane oxygenators. Intricate geometries are alsodifficult to achieve with conventional film and bubble oxygenators, asillustrated by the grid of plates in the film oxygenator in U.S. Pat.No. 3,070,092 to Wild et al. and the aluminum oxygenator tubes in U.S.Pat. No. 4,280,981 to Harnsberger.

Blood is a very delicate body tissue and is damaged when handled andexposed to foreign surfaces and gas atmospheres. Requiring the blood toflow through or around fibers or through tubes composed of substancessuch as aluminum or styrenes physically damage the blood by denaturationof proteins and mechanical damage to cells and formed elements.

In film and bubble oxygenators, the oxygen diffuses directly into theblood from the oxygen-rich atmosphere; carbon dioxide diffuses out ofthe blood to that atmosphere. In the membrane oxygenator, the oxygen andcarbon dioxide diffusion take place across a permeable membrane. Thedesign of the oxygenator, e.g., choice of membrane material, shouldmaximize the rate of gas exchange, that is, the rate of absorption ofthe oxygen by the blood without exposing the blood directly to a gasatmosphere.

It is apparent that a blood oxygenator which maximizes the rate of gasexchange may require a large exchange surface area and oxygenatorvolume, and may also damage the blood. The design parameters conflictsuch that optimizing one parameter may degrade another. Therefore, theproblem remains to optimize all the parameters to design a bloodoxygenator that has a large exchange surface area per unit volume, cantake on different geometries, minimizes damage to the blood, andmaximizes the rate of gas exchange.

The same conflicting parameters exist for other mass transfer devices,such as dialyzers. Dialyzers perform the function of removing metabolicwaste products without removal of essential constituents such asproteins. The problem to be solved here, analogous to that of bloodoxygenators, is to design a dialyzer which has a large exchange surfacearea per unit volume, can take on different geometries, minimizes damageto the blood, and maximizes the rate of removal of the waste productsfrom the blood.

Accordingly, prior to the development of the present invention, nosingle blood mass transfer device provided a large exchange surface areain a small volume capable of different geometries, and which minimizeddamage to the blood while providing a high rate of mass transfer. It istherefore an object of the present invention to provide a mass transferdevice which has a large exchange surface area in a small volume, andwhich minimizes damage to the blood while achieving a high rate of masstransfer. It is a further object of this invention to provide a bloodoxygenator which has a large exchange surface area in a small volume,and which minimizes damage to the blood while achieving a high rate ofgas exchange. It is a further object of this invention to provide ablood dialyzer which has a large exchange surface area in a smallvolume, and which minimizes damage to the blood while achieving a highrate of molecular transport. It is a feature of this invention to use apliable foam material in the mass transfer device as both the bloodpathway and the membrane across which the transfer occurs. It is anadditional feature of this invention that the blood mass transferdevices can take on varied and intricate geometries to satisfy therequirements of the particular application.

SUMMARY OF THE INVENTION

The present invention is a device for facilitating the exchange ofconstituents into and out of a fluid such as blood. The device includesa body of a pliable open-cell foam material. The open-cell structureforms channels through which the blood flows. These channels are formedof inter-connecting cells within the foam body lined by a skin (ormembrane) which forms as a consequence of the manner in which thematerial itself polymerizes. The paths of these channels through thefoam body are random and very varied or "tortuous." When blood is thefluid flowing through the channels, a polyurethane foam is preferabledue to its excellent blood handling properties.

The rest of the cells in the foam body are open and not sealed by thefoam membrane; these cells constitute the matrix of the material. In oneaspect of the invention, these cells form a gas pathway to allow oxygento migrate throughout the foam material and across the membrane into theblood while allowing carbon dioxide to migrate across the membrane outof the blood. Porous fibers can be used in the gas pathway portion ofthe foam body to more efficiently distribute oxygen throughout the foambody. The porous fibers are contained within the foam matrix and do notcome in contact with blood.

When configured as a blood oxygenator, a hydrophilic ("wettable") foamcan be used so that water from the plasma portion of blood wets themembrane. Oxygen and carbon dioxide are both carried in aqueoussolution, dissolved in the water portion of plasma, and are thereforeeasily transferred across the membrane.

In another aspect, the unsealed cells form a dialysate pathway fortransport of molecules out of the blood. The blood flows through theskinned channels and the molecules migrate across the skin membrane fromthe blood into the dialysate.

In a third aspect of the invention, the fluid flowing through theskinned channels can be a fluid other than blood. The unsealed portionof the foam body can then contain a gas, or another fluid, so that thegas or fluid constituents will migrate across the membrane into or outof the fluid in the skinned channels.

BRIEF DESCRIPTION OF THE DRAWINGS

Various objects, features, and advantages of the present invention willbe more fully appreciated as the same becomes better understood from thefollowing detailed description of the present invention when consideredin connection with the accompanying drawings, in which:

FIG. 1 shows a blood oxygenator comprising the foam material configuredas a cylinder;

FIG. 2 shows a cross section of a foam cylinder taken along line 2--2 inFIG. 1;

FIG. 3 shows an enlarged cross section of a foam cylinder taken alongline 3--3 in FIG. 1;

FIG. 4 shows a highly enlarged cross section of a porous fiber whichdistributes oxygen throughout the foam cylinder; and

FIG. 5 shows a cross section of a blood channel illustrating thediffusion across the skin membrane.

DETAILED DESCRIPTION OF THE DRAWINGS

With continuing reference to the drawing figures in which similarreference numerals are used throughout the description to describesimilar features of the invention, FIG. 1 shows a blood oxygenator 10configured with a foam cylinder 16 potted within a housing 18. The bloodcan enter through either access port 12 and flow through the oxygenatorwhile the oxygen can enter/exit through either access port 14, as thedesign is symmetrical.

The blood oxygenator 10 in FIG. 1 receives oxygen-poor (venous) bloodfrom the patient into access port 12 through devices and tubing whichare well known in the blood oxygenator art. Similarly, once the bloodhas been oxygenated, the oxygen-rich blood is returned to the patientvia well known devices. The oxygen source which is connected to theblood oxygenator 10 at access port 14 is also one commonly used in bloodoxygenation.

FIG. 2 shows a cross section of the foam cylinder 16 from FIG. 1. Thefoam cylinder comprises two series of voids which constitute twodistinct phases or portions of the foam. The first portion comprises thelarge voids which form the blood channels or blood pathway 30. The largevoids are interconnected and "skinned" with the foam material to form askinned layer or membrane 20 on the voids, thus forming channels. Thesechannels take on random, tortuous paths and define blood channels orblood pathway 30. Due to the random, tortuous paths of the bloodchannels 30, the blood pathway confines a large surface area in a smallvolume.

The second portion of the foam cylinder 16 comprises the smaller voidsof cells in the foam body which are not "skinned"; these cellsconstitute the matrix of the material. Some cells in this portion may beinterconnected, but all the cells in this portion are unsealed and formthe gas pathway 40 for the delivery of oxygen to and removal of carbondioxide from the blood. To minimize gas diffusion distances, hollowporous fibers 50 carry the gases throughout the foam cylinder to cutdown the diffusion distance between the source of the gas and the bloodpathway 30. The porous fibers 50 are shown in FIG. 2 and FIG. 3 asperpendicular to the blood pathway 30. However, the porous fibers arenot restricted to such a configuration and could be parallel or at anyangle to the blood pathway.

FIG. 3 shows a vertical cross section of the foam cylinder 16 whichillustrates the random and tortuous nature of the blood pathway 30. Theporous fibers 50 serve to distribute the gas within the foam cylinder tominimize the diffusion distance. The porous fibers are contained withinthe foam matrix and do not come in contact with blood. Without theporous fibers, oxygen would have to diffuse from the source on one sideof the foam cylinder, shown at 14 in FIG. 1, all the way through to theother side. The porous fibers act as a ventilation system to deliver theoxygen and remove the carbon dioxide throughout the foam cylinder moreefficiently.

As shown in FIG. 4, the fibers 50 are porous, thus allowing molecules topass into and out of the gas channel 52 through the pores 54. In thepreferred embodiment, the fiber is hydrophobic ("non-wettable") so nofluids pass into the fiber channel, with pore size sufficient to allowmolecules of oxygen and carbon dioxide to easily exit and enter theporous fibers. For example, porous fibers made of polyacrylonitrile canbe used, such as the DIAFLO™ ultra-filter XM50 sold by Amicon, which hasa pore size of 50,000 amu (atomic mass units).

FIG. 5 illustrates the process by which oxygenation takes place withinthe foam cylinder. A blood channel 30, defined by the skinned membrane20, is shown in FIG. 5. As the skinned membrane is hydrophilic, waterfrom the blood wets the skinned membrane to form a layer wetted withwater 22. As oxygen is soluble in water, the oxygen from the surroundinggas pathway or gas phase of the foam cylinder dissolves in the water ofthe wetted membrane 22 as shown by the arrow 60. Similarly, carbondioxide is also soluble in water, and the carbon dioxide in the bloodchannel 30 also dissolves in the water of the wetted membrane 22 asshown by the arrow 70. In this manner, water becomes the functionalmembrane and serves as the gas transport medium. Once dissolved in thewater, oxygen will then migrate into the blood and carbon dioxide willmigrate into the surrounding gas phase as a result of the diffusiongradient since both gases will be moving from an area of highconcentration to an area of low concentration. More particularly, carbondioxide is in high concentration in the blood and oxygen is in highconcentration in the gas phase of the foam cylinder. Therefore, adiffusion gradient is established such that oxygen will migrate from thegas phase into the blood in the blood channel, and carbon dioxide willmigrate from the blood in the blood channel to the gas phase of the foamcylinder. The wetted membrane 22 allows this transfer to take placeacross the membrane due to the solubility of the two gases in water.

In the preferred embodiment, the foam cylinder, or other foam body, iscomprised of a hydrophilic, polyurethane open cell foam such as HYPOL™5100. HYPOL™ foams are commercially available from W. R. Grace & Co.HYPOL™ foams have excellent blood handling properties. They arebiocompatible in that there is little chemical reaction with the bloodor tissues, or extraction into the blood of foreign material such asplasticizers. HYPOL™ 5100, configured as a foam cylinder as shown inFIG. 1, can be used with pressures comparable to human blood pressure,and above human blood pressure, as may be found in heart-lung machinecircuits.

HYPOL™ polymers are a family of foamable hydrophilic polyurethaneprepolymers derived from toluene diisocyanate or methylenediphenylisocyanate (MDI). HYPOL™ 5100 is one of the HYPOL™ PlusMDI-based prepolymers. In the production of polyurethane foams, excessisocyanate groups in the polymer react with water to produce carbondioxide which "blows" the foam at the same time that crosslinking isoccurring. This results in a crosslinked product containing bubbles oftrapped carbon dioxide. The "skin" forms as a consequence of phaseinterface phenomena because the gases that "blow", or form, the foamstructure are generated by chemical reaction between the pre-polymer andsolvent (water) within the material itself.

The porous fibers used to carry the gases in the blood oxygenatorembodiment are placed in with the reactants prior to adding the water orcarboxylic acids so that the reaction occurs around the porous fibers.In this way, the foam forms around the fibers, so that the fibers areincluded in the matrix of the foam. Additionally, surfactants such assilicone or Pluronic L-62 and P-75 (BASF Wyandotte Corporation) areadded so that the bubbles formed during the "blowing" process result ina three dimensional array of sealed, connected voids. The sealed,connected voids form random channels, each of which takes a tortuouspath. As a result, the foam body comprises a multiplicity of channelscontaining a large surface area in a small volume. Although the Figuresshow a foam cylinder, the foam can be produced in varied and intricategeometries and still comprise a multiplicity of channels containing alarge surface area in a small volume.

When configured as a blood oxygenator, the blood travels in the skinnedchannels and the second portion of the foam body contains the gaspathway, with diffusion of oxygen and carbon dioxide occurring acrossthe skin membrane. The foam body can also be configured to performdialysis by making a minor modification to the polymer molecular weightof the HYPOL™ foam. The foam with the modified molecular weight retainsits blood handling properties and the blood still flows through theskinned channels. However, the second portion of the foam body, thematrix, becomes a dialysate pathway rather than a gas pathway.

Dialysate is a solution of electrolytes and other naturally occurringsolutes at concentrations normally found in the blood at physiologicconcentration. The molecules of metabolic waste products (e.g., excesssodium or excess potassium, urea, creatinine, etc.) will migrate acrossthe skinned membrane from the blood to the dialysate phase because ofthe concentration gradient established. That is, the concentration inthe blood of sodium, potassium, and metabolic waste products is higherthan the concentration in the dialysate phase of the foam body. Wasteproducts from the blood (e.g., creatinine, urea, etc.) will migrateacross the membrane from the blood in the blood channel into thedialysate phase of the foam body because of the concentration gradient.That is, the concentration of waste products in the blood is higher thanthe concentration of the waste products in the dialysate phase of thefoam body. The molecular weight and resulting porosity of the foam areselected to allow transport across the membrane of low and middlemolecular weight molecules, but not protein molecules, which are large,complex molecules, and which must be retained within the blood.

The invention which is intended to be protected herein should not beconstrued as limited to the particular forms disclosed, as these are tobe regarded as illustrative rather than restrictive. For example, thefoam body could be used as any blood mass transfer device, and is notlimited to use as an oxygenator or dialyzer, and the geometries of thefoam body are not limited to a cylinder. Additionally, the foam bodycould be used as a mass transfer device between a fluid other thanblood, and another fluid or a gas.

Variations and changes may be made by those skilled in the art withoutdeparting from the spirit of the invention. Accordingly, the foregoingdetailed description should be considered exemplary in nature are notlimited to the scope and spirit of the invention as set forth in thefollowing claims.

What is claimed is:
 1. A biphasic foam structure comprising:a firstopen-celled phase formed of cells disposed within said foam structure; asecond phase formed by a permeable membrane which creates interconnectedcells to define a channel within said foam structure.
 2. A foamstructure according to claim 1 wherein said foam structure comprisespolyurethane.
 3. A foam structure according to claim 1 furthercomprising a plurality of porous fibers disposed within said firstphase.
 4. A blood oxygenator comprising:a body of hydrophilic, open-cellbiphasic foam; blood connection means connected to said body fortransporting blood into and out of said body; a first phase of said bodycomprising cells, said cells forming a gas pathway; a second phase ofsaid body formed by a gas permeable membrane comprised of said foamwhich creates interconnected cells to define a channel within said body,said channel forming a blood pathway, wherein said gas permeablemembrane separates said channel from said first phase so that water fromblood in said blood pathway wets said membrane such that oxygen withinsaid gas pathway dissolves in the water and carbon dioxide from theblood in said blood pathway dissolves in the water, whereby oxygen istransferred across said membrane into the blood and carbon dioxide istransferred across said membrane out of the blood.
 5. A blood oxygenatoraccording to claim 4, wherein said first phase of said body is comprisedof cells not sealed by said membrane.
 6. A blood oxygenator according toclaim 5, wherein said first phase of said body further comprises aplurality of porous fibers disposed within said body for distributingoxygen within said body.
 7. A blood oxygenator according to claim 4,wherein said second phase of said body further comprises a plurality ofsaid channels randomly disposed within said body, wherein each saidchannel follows a tortuous path.
 8. A blood oxygenator according toclaim 7, wherein said first phase of said body further comprises aplurality of porous fibers disposed within said body for distributingoxygen within said body.
 9. A blood mass transfer device comprising:abody of biphasic, open cell foam; blood connection means connected tosaid body for transporting blood into and out of said body; a firstphase of said body formed of cells within said body defining a firstpathway through said body for gas; a second phase of said body formed bya permeable membrane comprised of said foam which creates interconnectedcells to define a channel within said body, said permeable membraneseparating said channel from said first phase so that said channel formsa second pathway for blood.
 10. A blood mass transfer device accordingto claim 9, wherein said cells of said first phase are not sealed bysaid membrane.
 11. A blood mass transfer device according to claim 9,wherein said body of biphasic, open cell foam comprises hydrophilicfoam.
 12. A blood mass transfer device according to claim 9, whereinsaid channel follows a tortuous path.
 13. A blood mass transfer deviceaccording to claim 9, further comprising a plurality of said channelsrandomly disposed within said body.
 14. A blood mass transfer deviceaccording to claim 9, further comprising a plurality of said channelsrandomly disposed within said body, wherein each said channel follows atortuous path.
 15. A blood mass transfer device according to claim 9,wherein said body of biphasic, open cell foam comprises polyurethane.16. A blood mass transfer device according to claim 9, wherein saidpermeable membrane is gas permeable so that oxygen is transferred acrosssaid permeable membrane into the blood and carbon dioxide is transferredacross said permeable membrane out of the blood.
 17. A blood masstransfer device according to claim 16, wherein said body of biphasic,open cell foam comprises hydrophilic foam.
 18. A blood mass transferdevice according claim 16, further comprising means disposed within saidbody for distributing oxygen.
 19. A blood mass transfer device accordingto claim 18, wherein said means for distributing oxygen comprises aplurality of porous fibers.
 20. A blood mass transfer device accordingto claim 9, wherein said permeable membrane is permeable to metabolicwaste products so that waste products move out of the blood in saidblood pathway.